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Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study

  • M. Germana Orrù (a1), Antonella Baita (a1), Rossella Sitzia (a1), Alessandra Costa (a1), Elisabetta Muntoni (a1), Sabine Landau (a2), Luchino Chessa (a3), M. Giulia Farci (a3), Bernardo Carpiniello (a1) and Carmine M. Pariante (a2)...

Summary

Aims — Patients with chronic viral hepatitis suffer from a high prevalence of psychiatric problems. Furthermore, the treatment for chronic viral hepatitis, with interferon (IFN) alpha, induces the occurrence of further psychopathological symptoms. The autors examined whether patients with a pre-existing psychiatric diagnosis had more severe IFN alpha-induced psychiatric adverse effects, and whether they were more likely to interrupt the IFN alpha therapy, compared with control patients with no pre-existing psychiatric diagnosis. They also examined the psychopharmacological management of the interferon-alpha-induced psychiatric side effects. Methods — The authors studied prospectively 60 patients with chronic hepatitis B or C in Cagliari, Italy. Patients underwent psychiatric assessment before starting interferon alpha and monthly throughout the therapy. Results — After adjusting for the baseline psychopathology, there was no statistically significant difference in interferon-alpha-induced psychiatric adverse effects between patients with a pre-existing psychiatric diagnosis and controls. There was also no evidence that psychiatric cases were more likely than controls to interrupt the IFN alpha therapy because of psychiatric side effects. Moreover, there was no difference in the psychiatric adverse effects severe enough to require psychopharmacological treatment. Finally, psychopharmaco-logical management successfully treated psychiatric symptoms induced by the IFN alpha. Conclusions — Patients with a pre-existing psychiatric diagnosis do not have a specific vulnerability to interferon-alpha-induced psychiatric adverse effects.

Declaration of Interest: none of the authors have conflict of interests in writing this paper; CM. Pariante is funded by the UK Medical Research Council and by the NARSAD and the Guy's and St Thomas Charity

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Corresponding author

Address for correspondence: Dr. C.M. Pariante, Section of Clinical Neuropharmacology, PO Box 51, Institute of Psychiatry, King's College London, 1 Windsor Walk, London SES 8AF(United Kingdom). Fax: +44-20-7848.0051 E-mail: c.pariante@iop.kcl.ac.uk

References

Hide All
American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, (3rd ed. revised). American Psychiatric Press: Washington DC.
Beck, A.T., Ward, C.H., Mendelson, M., Mock, J. & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry 5, 561571.
Bonkovsky, H.L., Woolley, J.M. & The Consensus Interferon Group (1999). Reduction of health-related quality of life in chronic hepatitis C and improvement with interferon therapy. Hepatologx 29, 264270.
Byrne, G., Lehman, L., Kirshbaum, J., Borden, E., Lee, C. & Brown, R. (1986). Induction of tryptophan degradation in vitro and in vivo: a gamma interferon stimulated activity. Journal of Interferon hserach 6, 389396.
Capuron, L. & Ravaud, A. (1999). Prediction of the depressive effects of interferon-alpha-therapy by the patient's initial affective state. New England Journal of Medicine 340, 1370.
Capuron, L., Ravaud, A., Neveu, P.J., Miller, A.H., Maes, M. & Dantzer, R. (2002). Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Molecular Psychiatry 7, 468473.
Carpiniello, B., Orru, M.G., Baita, A., Pariante, C.M. & Farci, A.M.G. (1998). Mania induced by withdrawal ot treatment with Interferon Alfa. Archives of General Psychiatry 55, 8889.
Cassidy, E.M. & O'Keane, V. (2000). Depression and interferon alpha therapy. British Journal of Psychiatry 176, 494.
Dieperink, E., Willenbring, M. & Ho, S.B. (2000). Neuropsychiatric symptoms associated with hepatitis c and interferon-alpha: a review. American Journal of Psychiatry 157, 867876.
Dieperink, E., Ho, S.B., Tetrick, L., Dua, K. & Willenbring, M.L. (2004). Suicidal ideation during interferon-alpha 2b and ribavirin treatment of patients with chronic hepatitis C. General Hospital Psychiatry 26(3), 237.
Esteban, R. (1996). Managing patients on inteferon therapy. Digestive Disease and Science 41, 121S125S.
Fava, M., Guaraldi, G.P. & Mazzi, F. (1993). SCID: Intervista Clinica Strutturata per il DSM-III-R. Versione italiana. OS: Firenze [Spitzer R.L., Williams J.B., Gibbon M., First M.B. (1992). The Structured Clinical Interview for DSM-III-R (SCID). History, rationale and description. Archives of General Psychiatry 49, 624-629].
Gleason, O.C. & Yiates, W.R. (1999). Five cases of interferon alpha-induced depression treated with antidepressant therapy. Psvchosomatics 40, 510512.
Gleason, O.C., Yates, W.R., Isbell, M.D. & Philipsen, M.A. (2002). An open-label trial of citalopram for major depression in patients with hepatitis C. Journal of Clinical Psychiatry 63(3), 194198.
Goulding, C., O'Connell, P. & Murray, F.E. (2001). Prevalence of fibromyalgia anxiey and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition. European Journal Gastroenterology and Hepatology 13, 507511.
Guy, W. (1976). ECDEU Assessment Manual for Psychopharmacology. US Dept. of Health, Education and Welfare: Bethesda MD.
Hamilton, M. (1960). A rating scale for depression. Neurosurgery and Psychiatry 23, 5662.
Hauser, P. (2004). Neuropsychiatric side effects of HCV therapy and their treatment: focus on IFN-alpha-induced depression. Gastroenterolgy Clinics of North America 33, Suppl. 1, S3550.
Hauser, P., Soler, R., Reed, S., Kane, R., Gulati, M., Khosla, J., Kling, M.A., Valentine, A.D. & Meyers, C.A. (2000). Prophilactic treatment of depression induced by interfeon-alpha. Psvchosomatics 41, 439441.
Hauser, P., Khosla, J., Aurora, H., Laurin, J., Kling, M.A., Hill, J., Gulati, M., Thornton, A.L., Scultz, R.L., Valentine, A.D., Meyers, C.A. & Howell, C.D. (2002). A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorders in patients with hepatitis. Clinical Molecular Psychiatry 7, 942947.
Hensley, M.L., Peterson, B., Silver, R.T., Larson, R.A., Schiffer, C.A. & Szatrowsky, T.P. (2000). Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alpha-2b and low dose cylarabine for chronic myelogenous leukemia: analysis of cancer and leukmia group B 9013. Journal of Clinical Oncology 18, 13011308.
Ho, S.B., Nguyen, H., Tetrick, L.L., Opitz, G.A., Basara, M.L. & Dieperink, E. (2001). Influence of psychiatric diagnosis on interferon-alpha treatment of chronic hepatitis C in a veteran population. American Journal of Gastroenterologv 96, 157164.
Kraus, M.R., Schafer, A., Csef, H. & Scheurlen, M. (2002) Paroxetine for the treatment of interferon alpha induced depression in chronic hepatitis C. Alimentary Pharmacology and Therapeutics 16, 10911099.
Levenson, J.L. & Fallon, H.J. (1993). A treatment of depression caused by interferon-alpha. American Journal of Gaslroenterologx 88, 760761.
Loftis, J.M., Socherman, R.E., Howell, C.D., Whitehead, A.J., Hill, J.A., Dominitz, J.A. & Hauser, P. (2004). Association of interferon-alpha-induced depression and improved treatment response in patients with hepatitis C. Neuroscience Letter 365(2), 8791.
Mac Donald, E.M., Mann, A.H. & Thomas, H.C. (1987). Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant alpha-interferon in hepatitis-B-carriers. Lancet 2, 11751177.
Maddock, C. & Pariante, C.M. (2001). How does stress affect you? An overview of stress, immunity, depression and disease. Epidemiologia e Psichiatria Sociale 10(3), 153162.
Maddock, C., Baita, A., Orrii, M.G., Sitzia, R., Costa, A., Muntoni, E., Farci, M.G., Carpiniello, B. & Pariante, C.M. (2004). Psychopharmacological treatment of depression, anxiety, irritability and insomnia in patients receiving interferon alfa: a prospective case series and a discussion of biological mechanisms. Journal of Psychopharmacology 18(1), 4146.
Maddock, C., Landau, S., Barry, K., Maulayah, P., Hotopf, M., Cleare, A., Norris, S. & Pariante, C.M. (in press). Psychopathological symptoms during interferon- and ribavirin treatment: effects on virologic response. Molecular Psychiatry.
Malek-Ahmadi, P. & Ghandour, E. (2004). Bupropion for treatment of interferon-induced depression. Annals of Pharmacotherapy 38(7-8), 12021205.
Menkes, D.B. & Mac Donald, J.A. (2000). Interferons, serotonin and neurotoxicity. Psychological Medicine 30, 259268.
Meyers, C.A. & Valentine, A.D. (1995) Neurological and psychiatric adverse effects of immunological therapy. CNS Drugs 3, 5668.
Miller, A.H., Pariante, C.M. & Pearce, B.D. (1999). Effects of cytokines and glucocorticoid receptor expression and function: glucocorticoid resistance and relevance to depression. In Cytokines, Stress and Depression, (ed. Dantzer, R et al.), Kluwer Academic/plenum Plubishers: New York
Montgomery, S.A. (2002). Dopaminergic deficit and the role of amisulpiride in the treatment of mood disorders. International Clinical Psychopharmacology 17, Suppl 4, S915.
Mulder, R., Ang, M., Chapman, B., Ross, A., Stevens, I.F. & Edagar, C. (2000). Interferon treatment is not associated with a worsening of psychiatric symptoms in patients with hepatitis C. Journal of Gastroenterologv and Hepatology 15, 300303.
Musselman, D.L., Lawson, D.H., Gumnick, S.F., Manatunga, A.K., Penna, S., Goodkin, R.S., Greiner, K., Nemeroff, C.B. & Miller, A.H. (2001). Paroxetine for the prevention of depression induced by high-dose interferon alpha. New England Journal of Medicine 344, 961966.
Myiaoka, H., Otsubo, T.Kamijima, K., Ishii, M., Onuki, M. & Mitamura, K. (1999) Depression from interferon therapy in patients with hepatitis C. American Journal of Psychiatry 156, 1120.
Nagano, J., Nagasi, S., Sudo, N. & Kubo, C. (2004). Psychosocial stress, personality and the severity of chronic hepatitis C. Psxchosomatics 45(2), 100106.
Nozaki, O., Tkagi, C., Takaoka, K., Takata, T. & Yoshida, M. (1997). Psychiatric manifestations accompanying interferon therapy for patients with chronic hepatitis C: an overview of cases in Japan. Psychiatry and Clinical Neurosciences 51, 175180.
Pariante, C.M., Orru, M.G., Baita, A., Farci, M.G. & Carpiniello, B. (1999a). Treatment with IFN alfa in patients with Chronic Hepatitis and mood or anxiety disorders. Lancet 354, 131132.
Pariante, C.M., Pearce, B.D., Pisell, T.L., Sanchez, C.I., Po, C., Su, C. & Miller, A.H. (1999b). The pro-inflammatory cytokine, interleukin-1 alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 140, 43594366.
Pariante, C.M., Landau, S. & Carpiniello, B. (2002). Interferon alpha-induced neuropsychiatric adverse effect in patients with psychiatric diagnosis: a prospective, controlled study. New England Journal of Medicine 347(2), 148149.
Poynard, T., Leroy, V., Cohard, M., Thevenot, T., Mathurin, P., Opolon, P. & Zaesky, J.P. (1996). Meta analysis of interferon randomized trials in the treatment of viral hepatitis C: effects of dose and duration. Hepatology 24, 778789.
Renault, P.F., Hoofnagle, J.H., Park, Y., Mullen, K.D., Peters, M. & Jones, E.A. (1987). Psychiatric complications of long-term interferon alpha therapy. Archives of Internal Medicine 147, 15771580.
Russo, S., Boon, J.C., Korf, J. & Haagsma, E.B. (2003). Mirtazapine for the treatment of interferon-induced psychopathology. General Hospital Psychiatry 25(6), 497.
Schramm, T.M., Lawford, B.R., Mac Donald, G.A. & Cooksly, W.G. (2000). Sertraline treatment of ifn-alpha induced depressive disorders. Medical Journal of Australia 173, 359361.
Spielberg, C.D., Gorsuch, R.L. & Lushene, R.E. (1968). State-Trait Anxiety Inventory, Eorm X. Consulting Psychologist Press: Palo Alto.
Valentine, A.D., Meyers, C.A., Kling, M.A., Richelson, E. & Hauser, P. (1998). Mood and cognitive side effects of interferon-alpha therapy. Seminars in Oncology 25, Suppl 1, 3947.
Van Thiel, D.H., Friedlander, L., Molloy, P.J., Fagiuoli, S., Kania, R.J. & Caraceni, P. (1995). Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness. European Journal of Gastroenterology and Hepatology 7, 165168.
Wessely, S. & Pariante, C.M. (2002). Fatigue, depression and chronic hepatitis C infection. Psychological Medicine 32, 110.
Woo, M.H. & Burnakis, T.G. (1997). Interferon alfa in the treatment of chronic viral hepatitis B and C. Annals of Pharmacotherapy 31, 330337.

Keywords

Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study

  • M. Germana Orrù (a1), Antonella Baita (a1), Rossella Sitzia (a1), Alessandra Costa (a1), Elisabetta Muntoni (a1), Sabine Landau (a2), Luchino Chessa (a3), M. Giulia Farci (a3), Bernardo Carpiniello (a1) and Carmine M. Pariante (a2)...

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